SACITUZUMAB GOVITECAN for Non-small cell lung cancer|Brain metastases

Inclusion criteria

• {"criterion_text":"- 1.\tSigned informed consent must be obtained prior to participation in the study."}
• {"criterion_text":"- 10.\tAt least one untreated brain metastasis ≥ 5mm: a.\tPatients with largest measurable intracranial lesion ≥5 mm but <10 mm may be allowed to enroll upon agreement with the principal investigator (for patients with target lesions of ≥ 5mm but <10 mm, 1.5 mm slice thickness brain MRI is required). b.\tPrior local treatment is permissible provided unequivocal progression in the lesion has since occurred (discussed in neuro-oncology MDT) or if new lesions have occurred. c.\tFor at least 7 days prior to first dose of SG and bevacizumab in this study: Patient must be asymptomatic from CNS metastases and on a stable dose of corticosteroids, with a maximum of 4 mg dexamethasone/day. Anti-epileptic dose should also be stable for 7 days."}
• {"criterion_text":"- 11.\tParticipant must have recovered from all toxicities related to prior treatments to grade ≤ 1 (CTCAE v 5.0). Exception to this criterion are alopecia and neuropathy of any grades."}
• {"criterion_text":"- 12.\tAdequate organ function including the following laboratory values at the screening visit: ·\tAbsolute neutrophil count (ANC) ≥ 1.5 x 109/L (without growth factor support), ·\tPlatelets ≥ 100 x 109/L (without growth factor support), ·\tHemoglobin (Hb) ≥ 6 mmol/l (= 9 g/dl) (7 days without transfusions or growth factor support), ·\tAspartate transaminase (AST) ≤ 2.5 x ULN, or ≤ 5 × ULN if known liver metastases ·\tAlanine transaminase (ALT) ≤ 2.5 x ULN, or ≤ 5 × ULN if known liver metastases ·\tSerum albumin > 3 g/dL ·\tTotal bilirubin ≤ 1.5 ULN, ·\tCreatinine clearance ≥ 30 mL/min by calculation using Cockcroft-Gault formula or based on 24-hour urine sample assessment."}
• {"criterion_text":"- 13.\tParticipant is capable of following instructions regarding study treatment administration, and must be able to communicate with the Investigator and comply with the requirements of the study procedures."}
• {"criterion_text":"- 14.\tNegative serum or urine pregnancy test within 7 days prior to study treatment in women with childbearing potential. Patient must be willing to use effective methods of contraception. Female patients must be postmenopausal, surgically sterile, or they must agree to use a physical barrier method of contraception in addition to either an intrauterine device or hormonal contraception until at least 4 months after termination of study drug."}
• {"criterion_text":"- 2.\tParticipant is an adult ≥ 18 years of age at the time of informed consent."}
• {"criterion_text":"- 3.\tECOG performance status ≤1."}
• {"criterion_text":"- 4.\tEstimated life expectancy of 12 weeks or more."}
• {"criterion_text":"- 5.\tPathology proven metastatic non-squamous NSCLC"}
• {"criterion_text":"- 6.\tFor those without an actionable oncogenic driver: progression on immunotherapy and/or platinum-doublet chemotherapy (concurrent or sequential, in any order). If contra-indication for immunotherapy: progression on platinum-doublet chemotherapy."}
• {"criterion_text":"- 7.\tFor those with an actionable oncogenic driver: progression on targeted therapy and platinum-doublet chemotherapy. For the latter group, previous ICI is allowed but not mandatory."}
• {"criterion_text":"- 8.\tBM not in eloquent area (all patients have at least to be discussed with a neurologist, and preferably they are discussed in the local neuro-oncology MDT)."}
• {"criterion_text":"- 9.\tMaximum BM size 2 cm in longest diameter (for each BM)."}

Exclusion criteria

• {"criterion_text":"- 1.\tLeptomeningeal metastasis (based on MRI or CSF cytology, if strong suspicion despite negative MRI, CSF analysis should be done)."}
• {"criterion_text":"- 18.\tContra-indications specific to bevacizumab a.\tInadequately controlled hypertension (defined as systolic blood pressure > 150 mmHg and/or diastolic blood pressure > 100 mmHg). Anti-hypertensive therapy to achieve these parameters is allowable. b.\tPrior history of hypertensive crisis or hypertensive encephalopathy. c.\tSignificant vascular disease (e.g., aortic aneurysm requiring surgical repair or recent peripheral arterial thrombosis) within 6 months prior to start of treatment. d.\tHistory of hemoptysis (≥ one-half teaspoon of bright red blood per episode) within 1 month prior to start of treatment. e.\tEvidence of bleeding diathesis or coagulopathy (in the absence of therapeutic anticoagulation). f.\tCurrent or recent (within 10 days of start of treatment) use of aspirin (> 325 mg/day) or treatment with dipyridamole, ticlopidine, clopidogrel, and cilostazol. g.\tCurrent use of full-dose oral or parenteral anticoagulants or thrombolytic agents for therapeutic purposes that has not been stable for > 2 weeks prior to start of treatment. The use of full-dose oral or parenteral anticoagulants is permitted as long as the INR or aPTT is within therapeutic limits (according to the medical standard of the enrolling institution) and the patient has been on a stable dose of anticoagulants for at least 2 weeks prior to start of treatment. h.\tProphylactic anticoagulation for the patency of venous access devices is allowed, provided the activity of the agent results in an INR < 1.5 × ULN and aPTT is within normal limits within 14 days prior to start of treatment. i.\tProphylactic use of low-molecular-weight heparin (i.e., enoxaparin 40 mg/day) is permitted. j.\tCore biopsy or other minor surgical procedure, excluding placement of a vascular access device, within 7 days prior to the first dose of bevacizumab. k.\tHistory of abdominal or tracheoesophageal fistula or gastrointestinal perforation within 6 months prior to start of treatment. l.\tClinical signs of gastrointestinal obstruction or requirement for routine parenteral hydration, parenteral nutrition, or tube feeding. m.\tEvidence of abdominal free air not explained by paracentesis or recent surgical procedure. n.\tSerious, non-healing wound, active ulcer, or untreated bone fracture. o.\tProteinuria, as demonstrated by urine dipstick or > 1.0 g of protein in a 24-hour urine collection. All patients with ≥ 2+ protein on dipstick urinalysis at baseline must undergo a 24-hour urine collection and must demonstrate ≤ 1 g of protein in 24 hours. p.\tClear tumour infiltration into the thoracic great vessels is seen on imaging. q.\tClear cavitation of pulmonary lesions is seen on imaging."}
• {"criterion_text":"- 2.\tPrevious treatment with TROP2 inhibitor or angiogenesis inhibitor."}
• {"criterion_text":"- 3.\tKnown hypersensitivity to the study drugs, its metabolites, or formulation excipient."}
• {"criterion_text":"- 4.\tPositive serum pregnancy test or women who are breastfeeding."}
• {"criterion_text":"- 5.\tContra-indication for MRI."}
• {"criterion_text":"- 6. History of allogeneic bone marrow or solid organ transplant."}
• {"criterion_text":"- 7.\tHave had a prior anticancer biologic agent (ADC, ICI) within 4 weeks prior to enrolment or have had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to enrolment and have not recovered (ie, ≥ Grade 2 is considered not recovered) from AEs at the time of study entry. a.\tNote: Patients participating in observational studies are eligible."}
• {"criterion_text":"- 8.\tHave an active second malignancy. Note: patients with a history of malignancy that has been treated completely, with no evidence of active cancer for 3 years prior to enrollment, or patients with surgically cured tumours with low risk of recurrence (eg, nonmelanoma skin cancer, histologically confirmed complete excision of carcinoma in situ, or similar) are allowed to enroll."}
• {"criterion_text":"- 9.\tMet any of the following criteria for cardiac disease: a.\tMyocardial infarction or unstable angina pectoris within 6 months of enrollment. b.\tHistory of serious ventricular arrhythmia (ie, ventricular tachycardia or ventricular fibrillation), high-grade atrioventricular block, or other cardiac arrhythmias requiring antiarrhythmic medications (except for atrial fibrillation that is well controlled with antiarrhythmic medication); history of QT interval prolongation. c.\tNew York Heart Association (NYHA) class III or greater congestive heart failure or left ventricular ejection fraction of < 40%."}
• {"criterion_text":"- 10. Known hypersensitivity to iodinated contrast agents."}
• {"criterion_text":"- 10. Have active chronic inflammatory bowel disease (ulcerative colitis, Crohn’s disease) or GI perforation within 6 months of enrolment."}
• {"criterion_text":"- 11.\tHave active serious infection requiring antibiotics."}
• {"criterion_text":"- 12.\tHave known history of HIV-1 or 2 (or positive HIV-1/2 antibody, if done at screening) with detectable viral load OR taking medications that may interfere with SN-38 metabolism."}
• {"criterion_text":"- 13.\tHave known active hepatitis B virus (HBV) or hepatitis C virus (HCV). In patients with a history of HBV or HCV, patients with detectable viral loads will be excluded."}
• {"criterion_text":"- 14.\tHave other concurrent medical or psychiatric conditions that, in the investigator’s opinion, may be likely to confound study interpretation or prevent completion of study procedures and follow-up examinations."}
• {"criterion_text":"- 15.\tAny medical condition that, in the investigator’s or sponsor’s opinion, poses an undue risk to the patient’s participation in the study"}
• {"criterion_text":"- 16.\tUse of other investigational drugs (drugs not marketed for any indication) within 28 days or 5 half-lives (whichever is longer) of first dose of study drug."}
• {"criterion_text":"- 17.\tClinically severe pulmonary compromise resulting from intercurrent pulmonary illnesses including, but not limited to, any underlying pulmonary disorder (ie, pulmonary embolism within 1 months of enrolment, severe asthma, severe chronic obstructive pulmonary disease, restrictive lung disease, uncontrolled pleural effusion, etc.); any autoimmune, connective tissue, or inflammatory disorders with pulmonary involvement (ie, rheumatoid arthritis, Sjogren syndrome, sarcoidosis, etc.); or prior pneumonectomy."}

Primary endpoints

• {"endpoint_text":"- BM ORR (RANO-BM). This will be evaluated with MRI brain after six weeks of treatment and thereafter every six weeks. Confirmed BM ORR according to RANO-BM will be measured at 12 weeks.","definition_or_measurement_approach":"Measured using Response Assessment in Neuro-Oncology (RANO)-BM criteria with brain MRI after 6 weeks and every 6 weeks; confirmed BM ORR assessed at 12 weeks."}

Secondary endpoints

• {"endpoint_text":"- All imaging related endpoints will be measured with MRI brain for BM related outcomes and CT chest and upper abdomen for extracranial related outcomes after six weeks of treatment and thereafter every six weeks","definition_or_measurement_approach":"Imaging: MRI brain for brain metastases and CT chest/upper abdomen for extracranial disease; measured after 6 weeks and every 6 weeks."}
• {"endpoint_text":"- BM ORR (RANO-BM), with additional criteria for potential pseudo response due to bevacizumab","definition_or_measurement_approach":"Brain metastasis objective response rate per RANO-BM with extra criteria to account for possible pseudo-response from bevacizumab."}
• {"endpoint_text":"- BM DCR (RANO-BM), median CNS PFS (RANO-BM)","definition_or_measurement_approach":"Brain metastasis disease control rate and median CNS progression-free survival measured per RANO-BM."}
• {"endpoint_text":"- Extracranial ORR and DCR (RECIST 1.1).","definition_or_measurement_approach":"Extracranial objective response rate and disease control rate per RECIST 1.1."}
• {"endpoint_text":"- Median extracranial PFS (based on RECIST 1.1)","definition_or_measurement_approach":"Median progression-free survival for extracranial disease based on RECIST 1.1 assessments."}
• {"endpoint_text":"- Median overall PFS (based on RANO-BM for BM and RECIST 1.1 for extracranial lesions)","definition_or_measurement_approach":"Median overall progression-free survival combining RANO-BM assessments for brain and RECIST 1.1 for extracranial lesions."}
• {"endpoint_text":"- Median OS","definition_or_measurement_approach":"Median overall survival."}
• {"endpoint_text":"- Safety, evaluated with CTCAE v5.0 criteria during every visit","definition_or_measurement_approach":"Safety assessed at each visit using CTCAE version 5.0 criteria."}

Netherlands

Earliest CTIS Part Ii Submission Date

17-01-2025

Latest Decision Or Authorization Date

09-02-2026

Processing Time Days

388

Number Of Sites

3

Number Of Participants

25

Primary sponsor

Full Name

Academisch Ziekenhuis Maastricht

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Netherlands